A Phase I Study of Systemic Gene Therapy With SGT-94 in Patients With Solid Tumors (SGT94-01)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Systemic Gene Therapy With SGT-94 in Patients With Solid Tumors|
- Severity of Adverse Events [ Time Frame: 4 weeks each patient ] [ Designated as safety issue: Yes ]The severity of adverse experiences in each patient will be determined based upon changes in the results of clinical laboratory tests and physical examnations. These findings will be used to determine the safety and tolerability of increasing doses of SGT-94.
- Clinical Response [ Time Frame: Week 4 ] [ Designated as safety issue: No ]Clinical Response will be assessed according to standard criteria for the particular solid tumor. In general, Response Evaluation Criteria in Solid Tumors (RECIST) criteria will be used.
- Changes in Tumor Markers [ Time Frame: Week 4 ] [ Designated as safety issue: No ]When appropriate, changes in tumor markers between the values measured at baseline and at week 4 following the cycle of SGT-94 infusion will be assessed.
- Expression of RB94 in Tumor Biopsies [ Time Frame: Week 2 ] [ Designated as safety issue: No ]Tumor targeting and uptake of SGT-94 by the tumor cells will be determined using Immunohistochemistry to assess the expression of RB94 in any tumor biopsies obtained during the study.
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Dose escalation of experimental therapeutic SGT-94 to assess safety
SGT-94 will be given at doses of 0.6, 1.2, 2.4, 3.6 and 4.8 mgDNA/infusion(Doses 0-5, respectively)twice weekly for 3 weeks out of 4 in dose levels 0 to 4, and for 5 weeks out of 6 for dose level 5 (also 4.8mg DNA). Intravenous infusion will occur over 1 to 2.5 hours in 5% dextrose,with a final volume of SGT-94 and dextrose of 100 mL to 250 mL, depending on dose level.
RB94, a tumor suppressor gene, is a modified form of the retinoblastoma gene, RB110. RB94 has shown enhanced tumor suppressor and tumor cell killing activity compared to RB110 in all tumor cell types studied to date, including bladder cancer cell lines. Moreover, RB94 has shown no toxicity to any normal human cells tested.
SGT-94,the agent being tested, is a systemically administered complex composed of the RB94 gene (plasmid DNA)encapsulated in a liposome that is targeted to tumor cells by means of an anti-transferrin receptor single chain antibody fragment (TfRscFv)attached to the outside of the liposome. Pre-clinical in vivo efficacy studies have indicated that SGT-94, when systemically administered, preferentially targets tumor cells and efficiently transfects them. This results in cancer cell death via mechanisms that are unique for RB94 and also increases the tumor's response to conventional radiation and chemotherapy.
This Phase I study is designed to evaluate the safety of SGT-94 and to establish a practically attainable and/or tolerable dose of this anti-cancer agent for use in further clinical trials. Additionally, evidence of RB94 expression within tumor tissue after systemic administration of SGT-94 will be sought, and clinically observable anti-cancer effects in patients will be documented. Enrollment will be targeted to individuals with "RB negative" tumors, i.e. tumors in which there is no staining for RB protein by immunohistochemistry (IHC). Preference will be given to patients with tumors in a location amenable to biopsy following treatment with SGT-94. This would include the prostate, bladder, superficial lymph nodes and any mass suitable for fine needle aspiration under CT or ultrasound guidance, or any lesion reachable by endoscopy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01517464
|United States, Texas|
|University of Texas, M.D. Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Arlene Siefker-Radtke, M.D.||M.D. Anderson Cancer Center|